乳癌是世界上女性最常被診斷出的癌症類型之一。根據世界衛生組織的統計結果，全世界每年約有超過兩百萬名女性被診斷出乳癌。在我們先前研究中指出泛素特異性肽酶24 (ubiquitin-specific peptidase 24, USP24) 可以透過穩定含溴結構域的蛋白質去促進肺癌的惡化，而在肺癌晚期的時候USP24的表現量也會增加使得肺癌轉移和產生抗藥性。因此我們想要知道USP24在乳癌中所扮演的角色和分子機制。首先我們比較了MCF7和MDA-MB231兩種不同乳癌種類細胞株的USP24表現量，發現MCF7的USP24表現量比MDA-MB231還高。接著我們將細胞中的USP24表現量下降，透過傷口癒合試驗觀察其對細胞的影響。結果顯示下降USP24可以降低乳癌細胞的遷移能力。此外USP24抑制劑的處理也同樣可以降低乳癌細胞的遷移能力，而且USP24抑制劑還會透過自噬作用造成乳癌細胞的死亡。最後為了瞭解其中的分子機制，次世代RNA定序被用來比較細胞中有無USP24抑制劑治療的RNA差異。在MDA-MB231中，USP24抑制劑的處理會下降β-catenin的表現量，因此認為細胞遷移能力的下降，可能跟Wnt pathway有關。總而言之，USP24可能可以抑制乳癌細胞的遷移能力，了解USP24在乳癌當中的分子機制和USP24抑制劑可能有助於未來乳癌治療的發展。

Breast cancer is the most frequent cancer type for females. According to statistics from the World Health Organization, more than two millions women got breast cancer every year worldwide, and the mortality rate is still high. Although the regular therapy including surgery, radiotherapy, chemotherapy, hormone therapy and targeted therapy can decrease the mortality rate of breast cancer, drug resistance is the major problem for all the treatment therapy. Our recently studies showed that ubiquitin-specific peptidase 24 (USP24) can promote lung cancer malignancy by stabilizing bromodomain containing proteins and is involved in cancer metastasis and drug resistance. Therefore, targeting USP24 by using USP24 inhibitor, USP24-i, which was developed from our lab might be effective on inhibiting breast cancer. First, we studied the level of USP24 in cells and the samples from the breast cancer patients. Data indicated that the protein levels of USP24 in MCF7 is higher than MDA-MB231 and hormone receptor positive breast cancer tissue is also higher than triple-negative breast cancer tissue. Second, the roles of USP24 in cell growth and migratory ability of breast cancer was studied by knocking USP24 down. The results showed that knockdown of USP24 significantly inhibited the migration ability of breast cancer cells but also repressed cellular growth, implying that USP24 might positively regulate cell growth and metastasis of breast cancer. Third, USP24 inhibitor (USP24-i) was used to treat breast cancer cell lines to study the effect on cell growth and metastasis. Data revealed that USP24-i treatment not only inhibited the migration in breast cancer cell line but also led to cell death in MCF7 through autophagy pathway and MDA-MB231 through autophagy and apoptosis pathway, suggesting that targeting USP24 by the specific novel USP24 inhibitor, USP24-i, can inhibit breast cancer progression. Finally, to elucidate the molecular mechanism of USP24 in breast cancer, next generation RNA sequence is used to study different expression of RNA in USP24-i treatment or not. In conclusion, USP24 plays an important role in tumorigenesis and metastasis of breast cancer cells. Targeting USP24 by USP24-i significantly induced cell death and inhibiting cell migration. Understanding the molecular mechanism of USP24 in breast cancer and USP24-i may be a potential target to develop novel therapeutic strategy, which will be beneficial to the prevention of breast cancer in the future.

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